A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL-2,Journal of Medicinal Chemistry

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A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL-2
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-28 , DOI: 10.1021/acs.jmedchem.4c01117
Franziska Bannwart _{1,

2} , Leon F Richter ₃ , Simon Stifel ₃ , Johanna Rueter _{1,

2} , Holger N Lode ₄ , João D G Correia ₅ , Fritz E Kühn ₃ , Aram Prokop _{1,

2,

6}

Affiliation

From previous studies, it is evident that metal–organic gold(I) complexes have antiproliferative activities. The aim of this study is not only to find new anticancer agents but also to overcome existing cytostatic resistance in cancer cells. The synthesis and medicinal evaluation of two cationic 1,3-disubstituted gold(I) bis-tetrazolylidene complexes 1 and 2 are reported. To determine apoptosis-inducing properties of the complexes, DNA fragmentation was measured using propidium iodide staining followed by flow cytometry. Gold(I) complex 1 targets explicitly malignant cells, effectively inhibiting their growth and selectively inducing apoptosis without signs of necrosis. Even in cells resistant to common treatments such as doxorubicin, it overcomes multidrug resistance and sensitizes existing drug-resistant cells to common cytostatic drugs. It is assumed that gold(I) complex 1 involves the mitochondrial pathway in apoptosis and targets members of the BCL-2 family, enhancing its potential as a therapeutic agent in cancer treatment.

中文翻译：

一类新型金 (I) NHC 复合物对过度表达 BCL-2 的多药耐药白血病细胞具有促凋亡和再敏特性

从之前的研究来看，金属有机金（I）配合物显然具有抗增殖活性。这项研究的目的不仅是寻找新的抗癌药物，而且是克服癌细胞现有的细胞抑制耐药性。报道了两种阳离子1,3-二取代金(I)双四唑亚基配合物1和2的合成和药用评价。为了确定复合物的细胞凋亡诱导特性，使用碘化丙啶染色和流式细胞术测量 DNA 片段化。 Gold(I) 复合物1明确靶向恶性细胞，有效抑制其生长并选择性诱导细胞凋亡，而无坏死迹象。即使在对阿霉素等常见治疗方法产生耐药性的细胞中，它也能克服多药耐药性并使现有的耐药细胞对常见的细胞抑制药物敏感。据推测，金 (I) 复合物1涉及细胞凋亡中的线粒体途径并靶向 BCL-2 家族成员，从而增强了其作为癌症治疗药物的潜力。

更新日期：2024-08-28

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